Muscarinic potassium channels (KACh) are composed of two subunits, GIRK1 and GIRK4 (or CIR), and are directly gated by G proteins. We have identified a novel gating mechanism of KACh, independent of G-protein activation. This mechanism involved functional modification of KACh which required hydrolysis of physiological levels of intracellular ATP and was manifested by an increase in the channel mean open time. The ATP-modified channels could in turn be gated by intracellular Na+, starting at approximately 3 mM with an EC50 of approximately 40 mM. The Na(+)-gating of KACh was operative both in native atrial cells and in a heterologous system expressing recombinant channel subunits. Block of the Na+/K+ pump (e.g., by cardiac glycosides) caused significant activation of KACh in atrial cells, with a time course similar to that of Na+ accumulation and in a manner indistinguishable from that of Na(+)-mediated activation of the channel, suggesting that cardiac glycosides activated KACh by increasing intracellular Na+ levels. These results demonstrate for the first time a direct effect of cardiac glycosides on atrial myocytes involving ion channels which are critical in the regulation of cardiac rhythm.
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November 01 1996
Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.
J L Sui,
J L Sui
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
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K W Chan,
K W Chan
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
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D E Logothetis
D E Logothetis
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
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J L Sui
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
K W Chan
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
D E Logothetis
Department of Physiology and Biophysics, Mount Sinai School of Medicine, City University of New York, New York 10029, USA.
Online ISSN: 1540-7748
Print ISSN: 0022-1295
J Gen Physiol (1996) 108 (5): 381–391.
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J L Sui, K W Chan, D E Logothetis; Na+ activation of the muscarinic K+ channel by a G-protein-independent mechanism.. J Gen Physiol 1 November 1996; 108 (5): 381–391. doi: https://doi.org/10.1085/jgp.108.5.381
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